Possible association between ubiquitin-specific peptidase 46 gene and major depressive disorders in the Japanese population

Background: Several investigations have reported that abnormalities in circadian rhythms might be related to the pathophysiology of major depressive disorder (MDD) and the therapeutic response to selective serotonin reuptake inhibitors (SSRIs). Recently, ubiquitin-specific peptidase 46 (USP46), a new molecule related to the circadian clock system, has been described. We conducted a case control study between seven tagging SNPs (rs10517263, rs17675844, rs6554557, rs12646800, rs2244291, rs10034164, rs346005) in the USP46 gene, MDD, and the SSRI therapeutic response in MDD in the Japanese population. Method: We recruited 432 MDD patients (202 males and 230 females) and 792 healthy controls (319 males and 473 females). Two hundred sixty-one of 432 MDD patients were treated with SSRIs (fluvoxamine, sertraline or paroxetine). Result: We detected an association between the USP46 gene and MDD in a haplotype analysis (rs2244291-rs10034164-rs346005 and rs12646800-rs2244291-rs10034164-rs346005). However, we did not find any association between the USP46 gene and SSRI response or remission in MDD in the Japanese population. Limitations: A replication study using larger samples may be required for conclusive results, since our sample size was small. Conclusions: Our results suggest that the USP46 gene might play a role in the pathophysiology of MDD in the Japanese population.